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Matthew S McKinney, Anne W Beaven Division of Hematologic Malignancies, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Most cases of indolent non-Hodgkin lymphoma (NHL) are incurable with standard chemoimmunotherapy approaches, and patients with relapsed/refractory disease have progressively shorter remissions and short survival with subsequent chemotherapy regimens. This may potentially be overcome with diversification of treatment strategies to include other modalities including radiotherapy, small molecule signaling transduction inhibitors, or high-dose chemotherapy with stem cell support. Yttrium-90 ibritumomab tiuxetan (Zevalin®) is a novel treatment entity for indolent NHL. A radiolabeled antibody conjugate, it consists of a murine anti-CD20 antibody linked to a chelator molecule, tiuxetan, which is bound to radioactive yttrium. Yttrium-90 ibritumomab tiuxetan is approved for use as consolidation after initial treatment of follicular lymphoma as well as single-agent therapy in relapsed/refractory B-cell NHL. Responses are seen even in patients refractory to conventional cytotoxic chemotherapy and rituximab in both indolent and aggressive NHL subtypes. Recent clinical studies have also shown that yttrium-90 ibritumomab tiuxetan has significant activity when combined with novel targeted small molecular inhibitors as well as in autologous and allogeneic transplantation regimens. Here we review the biology underlying the efficacy of yttrium-90 ibritumomab tiuxetan in NHL and present an overview of the clinical experience with this agent in NHL. Finally, we discuss the current role of yttrium-90 ibritumomab tiuxetan in the armamentarium of treatments for NHL and possibilities for incorporating it into future NHL treatment algorithms. Keywords: non-Hodgkin lymphoma, indolent, CD20, radioimmunotherapy, ibritumomab tiuxetan

Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic delays. Here, we present evidence-based consensus guidelines for the diagnosis, monitoring, and management of erythropoietic protoporphyria and X-linked protoporphyria. A systematic literature review was conducted, and reviewed among subcommittees of experts, divided by topic. Consensus on guidelines was reached within each subcommittee and then among all members of the committee. The appropriate biochemical and genetic testing to establish the diagnosis is reviewed in addition to the interpretation of results. Prevention of symptoms, management of acute phototoxicity, and pharmacologic and nonpharmacologic treatment options are discussed. The importance of ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is discussed with management guidance. Finally, management of pregnancy and surgery and the safety of other therapies are summarized. We emphasize that these are multisystemic disorders that require longitudinal monitoring. These guidelines provide a structure for evidence-based diagnosis and management for practicing physicians. Early diagnosis and management of these disorders are essential, particularly given the availability of new and emerging therapies.

Danielle M Brander, Anne W BeavenDuke University Medical Center, Durham, NC, USAAbstract: Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade®), a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies. Several clinical trials were conducted with bortezomib for the treatment of non-Hodgkin’s lymphoma. As a single agent, overall responses in follicular lymphoma varied greatly (16%–41%), with weekly bortezomib showing less neurotoxicity than twice-weekly regimens, but with concern about decreased responses. Combination with rituximab was projected to improve the efficacy of bortezomib, but this resulted in increased toxicities and questionable added benefit. Although the largest Phase III study in follicular lymphoma of bortezomib plus rituximab versus rituximab alone demonstrated a significant progression-free survival difference, the absolute difference was small (12.8 months versus 11 months). Combining bortezomib with established regimens, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), or rituximab-bendamustine also did not show definite benefit, and many of these studies did not meet their primary endpoint when bortezomib failed to improve responses or survival to the degree anticipated. In a disease where the goal of treatment is palliative and affected patients often have other medical and treatment-related comorbidities, decisions regarding therapies which carry risks of additional toxicities must be considered carefully. Conclusive evidence of the ability of bortezomib to improve patient outcomes meaningfully and to justify the added toxicity is lacking, but limitations in cross-trial comparisons are recognized. Large randomized trials and investigations of combinations with promising novel targeted agents will aid in determining the role of bortezomib, if any, in the future treatment of follicular lymphoma.Keywords: bortezomib, follicular lymphoma, proteasome inhibitor

Purpose: Continuous-glucose-monitoring (CGM) sensors provide near-real-time glucose data and have been introduced commercially as a tool to inform nutrition decisions. The aim of this pilot study was to explore how factors such as the menstrual phase, extended running duration, and carbohydrates affect CGM outcomes among trained eumenorrheic females in an outdoor simulated ultraendurance running event. Methods: Twelve experienced female ultrarunners (age 39 [6] y) participated in this crossover study. Participants completed an ultraendurance simulation run of 4 hours in the midfollicular and midluteal phases of their menstrual cycle, which consisted of a 3-hour fasted outdoor run (FASTED) followed by a 1-hour treadmill run (TREAD), where 3 standardized 20-g oral glucose doses were provided. Results: Using a mixed linear model, the menstrual phase was statistically significant for differences in glucose measurements from CGM compared with capillary glucose sampling during TREAD (P =.02) but not FASTED. Additionally, the CGM sensor reported glucose levels with an average of −0.43 mmol·L−1 (95% CI, − 0.86 to −0.005) and −1.02 mmol·L−1 (95% CI, −1.63 to −0.42) lower in fasted and fed scenarios, respectively, when compared with capillary glucose. Conclusion: CGM underreports capillary glucose during fasted and fed exercise. Factors contributing to this underreporting between the sampling methods (CGM vs capillary) were dependent on a combination of exogenous glucose availability, individual biological differences, and the menstrual phase. [ABSTRACT FROM AUTHOR]

Urban green spaces (UGS) mitigate negative impacts of urban living and provide positive effects on citizens’ mood, health and well-being. The net effect of UGS on wildlife health and human welfare remains understudied in urban zones proximal to wildlife rich areas. This study assessed the concomitant relationship between the environment and health of wildlife in Hwange Town in Zimbabwe through a questionnaire survey from June—December 2022. This study aimed to: i) assess the local perceptions on the link between urban ecology and urban ecosystems relative to wildlife health, ii) determine the local perceptions on the changes in the areal extent of green spaces, and iii) examine local perceptions towards green spaces and human-wildlife conflict in Hwange Town. Locals indicated that agricultural activities, urbanisation, mining and poaching were destroying and polluting the natural habitat. Increased magnitude, impact and frequency of wildlife-human conflicts signals increasing depletion of green spaces and expansion of urbanisation into wildlife habitats. There was no statistically significant correlation (r = 0.088; p = 0.172) in the local perceptions on the relation between ecosystem and well-being of wildlife. The urban ecosystem mosaic complex is unpredictable, heterogenous and evolving with human activities imploring a need for optimisation of human-activities and wildlife wellbeing. However, without financial and infrastructural support local communities are unable to conserve wildlife. We suggest community-based wildlife protection programmes integrating citizen science data (local ecological knowledge) using existing information communication platforms as alternative options to sustain wildlife conservation in urban green spaces in wildlife rich developing towns.

Small-scale fisheries support numerous livelihoods in Zimbabwe. However, men are the key actors in the fishing sector relegating women to peripheral roles, often, diminishing women’s contribution to household economy and food security. This study investigated the(i) gendered nature of rod and line angling fisheries, (ii) drivers and barriers for gender roles and participation in rod and line angling fisheries, and (iii) household contribution of rod and line angling fisheries in Lake Kariba. The level of participation in fishing, and postharvest roles such as gutting, gleaning, drying, and smoking significantly differs (p 0.05) influence the opinions of the fishers towards the drivers and barriers for engaging in rod angling. Women dominate men in numbers and the roles they play, though they have inadequate decision-making powers and hardly get the recognition they deserve in the rod and line angling value chain in Lake Kariba. Developing a pro-women National Fisheries and Aquaculture Policy in Zimbabwe will uplift and empower women fishers in contributing to household food security and poverty alleviation in small-scale artisanal fisheries.

Temminck’s pangolin, Smutsia temminckii (Smuts, 1832) is a threatened but protected species in Zimbabwe whose population is declining, ostensibly, due to poaching and persecution by humans. Inasmuch as the human factor is a critical dimension in Temminck’s pangolin population dynamics, there are few studies documenting local perceptions on conservation threats and options for the species in Zimbabwe. The study aimed to (a) assess the conservation perceptions of local fringe communities and (b) explore existing and potential conservation options for Temminck’s pangolin in Hwange National Park (HNP) in Zimbabwe. Data on local perceptions towards Temminck’s pangolin were collected through a questionnaire survey from May to December 2021, delving across cultural, political, economic, and social aspects in HNP. Poaching and trafficking, spurred by lucrative market prices and frivolous superstitious cultural beliefs and myths associated with the species and its by-products, are the apex drivers for Temminck’s pangolin dynamics in HNP. Climate change and habitat degradation mostly by African savanna elephants also affect Temminck’s pangolin populations in the HNP. A multifaceted conservation approach integrating indigenous knowledge systems, citizen science data, active community involvement, modern conservation methods, and a zero pangolin poaching policy in HNP is imperative for Temminck’s pangolin conservation.

Abstract Background Maintaining a consistent sleep and wake time is often reported as a key component of circadian rhythmicity and quality sleep. However, the impact of sleep onset and offset time variability on overall sleep outcomes are underreported in elite athlete populations. This study investigated the relationship between sleep onset and offset time variability using the sleep regularity index (SRI) and measures of sleep and well-being in professional rugby union athletes. Twenty-three professional male rugby union athletes (mean ± SD, age: 23 ± 3 y) underwent sleep monitoring via wrist actigraphy for three weeks during a pre-season phase of training and completed a daily wellness questionnaire. Median SRI was calculated and used to stratify the trainees into two quantile groups: >76.4 SRI (Regular, n = 11) and

Background/objectives: Team sports are characterised by repeated maximal intensity bursts of activity, requiring significant energy contribution from the phosphagen pathways. The objective of this study was to evaluate the impact of different rest periods on repeated maximal intensity efforts. Methods: The effect of three different recovery periods (60 s, 90 s and 120 s) during a 10 × six-seconds intermittent sprint training protocol performed on a cycle ergometer was investigated. Thirteen part-time female athletes from two sports, Rugby Sevens and Netball competing for their state participated in the study. Peak Power (PPO), Mean Power (MPO), “total work” in the form of calorie expenditure, performance decrement, repetitions over 95% PPO, blood lactate, and RPE were recorded. Results: There was a significant effect of condition on MPO and calorie expenditure (p

BackgroundThe fecal immunochemical test (FIT) is the primary modality used by the Los Angeles County Department of Health Services (LADHS) for colorectal cancer (CRC) screening in average-risk patients. Some patients referred for FIT-positive diagnostic colonoscopy have neither adenomas nor more advanced pathology. We aimed to identify predictors of false-positive FIT (FP-FIT) results in our largely disenfranchised, low socioeconomic status population.MethodsWe conducted a retrospective study of 596 patients who underwent diagnostic colonoscopy following a positive screening FIT. Colonoscopies showing adenomas (or more advanced pathology) were considered positive. We employed multiple logistic and linear regression as well as machine learning models (MLMs) to identify clinical predictors of FP-FIT (primary outcome) and the presence of advanced adenomas (secondary outcome).ResultsOverall, 268 patients (45.0%) had a FP-FIT. Female sex and hemorrhoids (odds ratios [ORs] 1.59 and 1.89, respectively) were associated with increased odds of FP-FIT and fewer advanced adenomas (β = - 0.658 and  - 0.516, respectively). Conversely, increasing age and BMI (ORs 0.94 and 0.96, respectively) were associated with decreased odds of FP-FIT and a greater number of advanced adenomas (β = 0.073 and 0.041, respectively). MLMs predicted FP-FIT with high specificity (93.8%) and presence of advanced adenoma with high sensitivity (94.4%).ConclusionIncreasing age and BMI are associated with lower odds of FP-FIT and greater number of advanced adenomas, while female sex and hemorrhoids are associated with higher odds of FP-FIT and fewer advanced adenomas. The presence of the aforementioned predictors may inform the decision to proceed with diagnostic colonoscopy in FIT-positive patients.

Despite the importance of strength and power in rugby skills and match outcomes, there exists a noticeable gap in the measurement consistency and estimation of a true change of typical assessments designed to assess these qualities. To address this gap, we investigated the between-session reliability, interrelationships, and minimal detectable changes (MDC) of commonly used strength and power measures in team sports. Sixteen national-level rugby 7 s players were tested on two occasions, one week apart. Both the best and average (of 2–3 trials) peak force, peak power, height, distance, and/or strength indices during countermovement jump (CMJ), drop jump (DJ), isometric mid-thigh pull (IMTP), plyometric push-up (PPU), and standing long jump (SLJ) were obtained. Furthermore, one-repetition maximum (1RM) strength for bench press and back squat, reactive strength index, and dynamic strength index were also determined. Reliability was assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV), and used for MDC calculations, and interrelationships between variables were determined using correlation coefficients. Reliability was excellent for bench press, back squat, and SLJ (ICCs > 0.91); high to excellent for IMTP peak force, all CMJ, and DJ (except best DJ height and contact time), and PPU peak force parameters (ICCs > 0.78), with < 10% CVs (except PPU peak power). MDCs were generally smaller for average than best values. Large to very large relationships (r = 0.60 to 0.85) were observed between bench press, back squat, and IMTP with selected parameters of CMJ and PPU (p < 0.05), but not in DJ and SLJ. In conclusion, selected measures of strength and power displayed high to excellent reproducibility, with average values (rather than best) offering more stable assessments, and “smaller” MDCs. Based upon the relationships, it can be inferred that maximising strength would likely contribute to enhanced explosive performance.